Genome-Wide Association Studies in Dogs and Humans Identify ADAMTS20 as a Risk Variant for Cleft Lip and Palate

Cleft lip with or without cleft palate (CL/P) is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR) breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10-13; adjusted p= 2.2 x 10-3). Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 – 10.73 Mb) segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS) in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3)), which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM) of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10-6) with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans

Laboratory layered latte

Inducing thermal gradients in fluid systems with initial, well-defined density gradients results in the formation of distinct layered patterns, such as those observed in the ocean due to double-diffusive convection. In contrast, layered composite fluids are sometimes observed in confined systems of rather chaotic initial states, for example, lattes formed by pouring espresso into a glass of warm milk. Here, we report controlled experiments injecting a fluid into a miscible phase and show that, above a critical injection velocity, layering emerges over a time scale of minutes. We identify critical conditions to produce the layering, and relate the results quantitatively to double-diffusive convection. Based on this understanding, we show how to employ this single-step process to produce layered structures in soft materials, where the local elastic properties vary step-wise along the length of the material

Team-taught versus individually taught undergraduate education: A qualitative study of student experiences and preferences

Team teaching is becoming more common in undergraduate programmes of study although the relative merits to the more traditional individually taught courses have not been determined for best practice. For this study, 15 final year undergraduate students were interviewed to gain insight into their learning experiences. A thematic analysis of the interview data identified the perceived advantages and disadvantages of each mode of teaching. The advantages of individually taught courses included: Consistency of content delivery and advice, Familiarity with the lecturer’s teaching style and better Continuity of the subject content. The disadvantage of individually taught modules included Missing knowledge, compared to a team approach. Advantages of team taught modules included: Greater insight into a topic delivered by multiple team members. Disadvantages included: Content overlap, Conflicting messages relating to assessment, team members not taking Ownership of their roles and responsibilities and a belief that overall Team failure is worse than individual failure to deliver a module well. The results revealed that individually taught modules were generally preferred to team taught modules. A set of best practice recommendations are proposed to address the challenges when delivering team-taught teaching and become more student focused

Contemporary review of risk-stratified management in acute uncomplicated and complicated diverticulitis

BACKGROUND: Acute colonic diverticulitis is a common clinical condition. Severity of the disease is based on clinical, laboratory, and radiological investigations and dictates the need for medical or surgical intervention. Recent clinical trials have improved the understanding of the natural history of the disease resulting in new approaches to and better evidence for the management of acute diverticulitis. METHODS: We searched the Cochrane Library (years 2004-2015), MEDLINE (years 2004-2015), and EMBASE (years 2004-2015) databases. We used the search terms "diverticulitis, colonic" or "acute diverticulitis" or "divertic*" in combination with the terms "management," "antibiotics," "non-operative," or "surgery." Registers for clinical trials (such as the WHO registry and the https://clinicaltrials.gov/) were searched for ongoing, recruiting, or closed trials not yet published. RESULTS: Antibiotic treatment can be avoided in simple, non-complicated diverticulitis and outpatient management is safe. The management of complicated disease, ranging from a localized abscess to perforation with diffuse peritonitis, has changed towards either percutaneous or minimally invasive approaches in selected cases. The role of laparoscopic lavage without resection in perforated non-fecal diverticulitis is still debated; however, recent evidence from two randomised controlled trials has found a higher re-intervention in this group of patients. CONCLUSIONS: A shift in management has occurred towards conservative management in acute uncomplicated disease. Those with uncomplicated acute diverticulitis may be treated without antibiotics. For complicated diverticulitis with purulent peritonitis, the use of peritoneal lavage appears to be non-superior to resection

The Influence of Social Comparison on Visual Representation of One's Face

Can the effects of social comparison extend beyond explicit evaluation to visual self-representation—a perceptual stimulus that is objectively verifiable, unambiguous, and frequently updated? We morphed images of participants' faces with attractive and unattractive references. With access to a mirror, participants selected the morphed image they perceived as depicting their face. Participants who engaged in upward comparison with relevant attractive targets selected a less attractive morph compared to participants exposed to control images (Study 1). After downward comparison with relevant unattractive targets compared to control images, participants selected a more attractive morph (Study 2). Biased representations were not the products of cognitive accessibility of beauty constructs; comparisons did not influence representations of strangers' faces (Study 3). We discuss implications for vision, social comparison, and body image

Population structure and linkage disequilibrium unravelled in tetraploid potato

Association mapping is considered to be an important alternative strategy for the identification of quantitative trait loci (QTL) as compared to traditional QTL mapping. A necessary prerequisite for association analysis to succeed is detailed information regarding hidden population structure and the extent of linkage disequilibrium. A collection of 430 tetraploid potato cultivars, comprising two association panels, has been analysed with 41 AFLP® and 53 SSR primer combinations yielding 3364 AFLP fragments and 653 microsatellite alleles, respectively. Polymorphism information content values and detected number of alleles for the SSRs studied illustrate that commercial potato germplasm seems to be equally diverse as Latin American landrace material. Genome-wide linkage disequilibrium (LD)—reported for the first time for tetraploid potato—was observed up to approximately 5 cM using r2 higher than 0.1 as a criterion for significant LD. Within-group LD, however, stretched on average twice as far when compared to overall LD. A Bayesian approach, a distance-based hierarchical clustering approach as well as principal coordinate analysis were adopted to enquire into population structure. Groups differing in year of market release and market segment (starch, processing industry and fresh consumption) were repeatedly detected. The observation of LD up to 5 cM is promising because the required marker density is not likely to disable the possibilities for association mapping research in tetraploid potato. Population structure appeared to be weak, but strong enough to demand careful modelling of genetic relationships in subsequent marker-trait association analyses. There seems to be a good chance that linkage-based marker-trait associations can be identified at moderate marker densities

The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery

The International Human Epigenome Consortium (IHEC) coordinates the generation of a catalog of high-resolution reference epigenomes of major primary human cell types. The studies now presented (see the Cell Press IHEC web portal at http://www.cell.com/consortium/IHEC) highlight the coordinated achievements of IHEC teams to gather and interpret comprehensive epigenomic datasets to gain insights in the epigenetic control of cell states relevant for human health and disease

Saturated Fats: A Perspective from Lactation and Milk Composition

For recommendations of specific targets for the absolute amount of saturated fat intake, we need to know what dietary intake is most appropriate? Changing agricultural production and processing to lower the relative quantities of macronutrients requires years to accomplish. Changes can have unintended consequences on diets and the health of subsets of the population. Hence, what are the appropriate absolute amounts of saturated fat in our diets? Is the scientific evidence consistent with an optimal intake of zero? If not, is it also possible that a finite intake of saturated fats is beneficial to overall health, at least to a subset of the population? Conclusive evidence from prospective human trials is not available, hence other sources of information must be considered. One approach is to examine the evolution of lactation, and the composition of milks that developed through millennia of natural selective pressure and natural selection processes. Mammalian milks, including human milk, contain 50% of their total fatty acids as saturated fatty acids. The biochemical formation of a single double bond converting a saturated to a monounsaturated fatty acid is a pathway that exists in all eukaryotic organisms and is active within the mammary gland. In the face of selective pressure, mammary lipid synthesis in all mammals continues to release a significant content of saturated fatty acids into milk. Is it possible that evolution of the mammary gland reveals benefits to saturated fatty acids that current recommendations do not consider